NEW YORK – Women whose screening mammograms produce false alarms have a heightened risk of being diagnosed with breast cancer years later, but the reason remains mysterious, researchers say.

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An increased risk of breast cancer among women with a “false positive” mammogram has been reported before. What’s new about this study is that the authors tried to figure out how much, if any, of the extra risk is simply due to doctors missing the cancer the first time they investigated the worrisome mammogram findings.

But mistakes from doctors missing cancers explained only a small percentage of the increased risk, according to lead author My von Euler-Chelpin, an epidemiologist from the University of Copenhagen in Denmark.

She told Reuters Health in a telephone interview that she could not explain most of the increased risk of later breast cancer in women with false-positive mammograms. (A mammogram is considered false positive when it suggests possible breast cancer but additional screenings or a biopsy fails to find it.)

Of more than 58,000 Danish women who had mammography between 1991 and 2005, her study identified 4,743 women with suspicious findings that were eventually declared negative.

By 2008, 295 of those 4,743 women had been diagnosed with breast cancer, von Euler-Chelpin and colleagues reported in Cancer Epidemiology.

Radiologists reread the original mammograms and found that doctors had actually missed the cancer in 72 of the 295 women, for a false-negative rate of 1.5 percent. Even after taking those missed cancers into account, however, the researchers found that women with false-positive mammograms were still 27 percent more likely to be diagnosed with breast cancer years later, compared to women with only negative test results.

The risk was slightly higher in women who had surgical biopsies that turned out to be negative.

Von Euler-Chelpin thinks a smaller percentage of American women would have an elevated risk for breast cancer after a false-positive test because the U.S. has a higher rate of false positives than Denmark. The risk of a false-positive test over 10 mammograms ranges from 58 percent to 77 percent in the U.S., while it is around 16 percent in Denmark, the study says.

Dr. Michael Alvarado, a breast cancer surgeon from the University of California, San Francisco, agreed that the risk of being diagnosed with breast cancer after a false positive mammogram is probably lower in the U.S. than in Denmark.

“It’s hard to translate the data to the U.S. population because we have such a different screening program, we tend to biopsy everything, and we’re much more aggressive,” he told Reuters Health. Alvarado was not involved in the current study.

“Is there some inherent biology of the breast that makes it suspicious and it puts you at higher risk? I don’t think anyone knows what it is,” he said.

Alvarado wondered if women who get false-positive mammograms should be followed more closely by their doctors, or if false-positive patients should be screened differently.

Von Euler-Chelpin told Reuters Health the excess rate of breast cancer among women who have had false-positive mammograms points to the need to personalize screening programs for women - and Dr. Karla Kerlikowske agreed.

Kerlikowske, from the University of California, San Francisco, is developing a risk calculator app to guide women in deciding how often to get mammograms. The calculator considers a range of factors, including age, race, previous breast cancer, family history and breast density. Kerlikowske was not involved in the current study.

Although having had a false-positive mammogram is associated with a woman’s breast cancer risk, Kerlikowske points out that the actual risk of being diagnosed with breast cancer remains low.

The average five-year breast cancer risk for a 50-year-old white woman with no prior family history of breast cancer is 1.25 percent, the calculator shows. It ranges from less than 1 percent, to 2.70 percent, depending upon breast density, for the same woman with a history of a prior breast biopsy, regardless of whether the biopsy was positive or negative.

“The absolute risk is still small,” Kerlikowske said. “To me, it just says, now you have this risk factor, and you have to consider it with other risk factors.”

Von Euler-Chelpin agrees.

“This paper is one little step on the way of trying to identify high-risk groups,” she said. “The goal is to find more personalized screening programs for women.”

The American Cancer Society recommends that women be screened for breast cancer every year they are in good health starting at age 40. But a growing number of researchers have questioned the benefits of annual mammograms, and since 2009 the government-backed United States Preventive Services Task Force has recommended that screening be done every two years and be generally restricted to women aged 50 to 74.

Women in Denmark between the ages 50 to 69 are invited to have screening mammograms every other year, Von Euler-Chelpin said.

Getting a mammogram every other year instead of annually did not increase the risk of advanced breast cancer in women ages 50 to 74, according to a study Kerlikowske published last year. (see Reuters story of March 18, 2013 here: http://reut.rs/1w7CMuh)

The recommendation to reduce the frequency and delay the start of mammography screening was based on research showing the risk of false-positive results – which needlessly expose women to the anguish of a possible breast cancer diagnosis and the ordeal of further testing – outweighed the benefits of detecting cancers earlier.